, Volume 5, Issue 4, pp 229–238 | Cite as

Mutation in the gene encoding lysosomal acid phosphatase (Acp2) causes cerebellum and skin malformation in mouse

  • Ashraf U. Mannan
  • Elena Roussa
  • Cornelia Kraus
  • Micheal Rickmann
  • Joerg Maenner
  • Karim Nayernia
  • Kerstin Krieglstein
  • André Reis
  • Wolfgang EngelEmail author
Original Article


We report a novel spontaneous mutation named nax in mice, which exhibit delayed hair appearance and ataxia in a homozygote state. Histological analyses of nax brain revealed an overall impairment of the cerebellar cortex. The classical cortical cytoarchitecture was disrupted, the inner granule cell layer was not obvious, the Purkinje cells were not aligned as a Purkinje cell layer, and Bergmann glias did not span the molecular layer. Furthermore, histological analyses of skin showed that the hair follicles were also abnormal. We mapped the nax locus between marker D2Mit158 and D2Mit100 within a region of 800 kb in the middle of chromosome 2 and identified a missense mutation (Gly244Glu) in Acp2, a lysosomal monoesterase. The Glu244 mutation does not affect the stability of the Acp2 transcript, however it renders the enzyme inactive. Ultrastructural analysis of nax cerebellum showed lysosomal storage bodies in nucleated cells, suggesting progressive degeneration as the underlying mechanism. Identification of Acp2 as the gene mutated in nax mice provides a valuable model system for studying the role of Acp2 in cerebellum and skin homeostasis.


Mutant mouse strain Genetic linkage Cerebellum Hair follicle Lysosomal storage diseases 



This work was funded by the Deutsche Forschungsgemeinschaft through the DFG-Research Center for Molecular Physiology of the Brain to W.E. and M.R. The authors would like to thank S. Zimmermann for operational help, M. Wahl for assistance with structural biology programs, and K. von Figura for useful discussions and helping us with Acp2 enzymatic assay. A. Eberwein, M. Moeschner, and M. Steckel for technical assistance, and our animal housekeepers for breeding and maintaining these mice.

Supplementary material

Table S1 Summary of genes reported in nax locus

supp.pdf (12 kb)
(PDF 13 KB)


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Ashraf U. Mannan
    • 1
  • Elena Roussa
    • 2
  • Cornelia Kraus
    • 3
  • Micheal Rickmann
    • 2
  • Joerg Maenner
    • 2
  • Karim Nayernia
    • 1
  • Kerstin Krieglstein
    • 2
  • André Reis
    • 3
  • Wolfgang Engel
    • 1
    Email author
  1. 1.Institute of Human GeneticsUniversity of GoettingenGoettingenGermany
  2. 2.Center of AnatomyUniversity of GoettingenGermany
  3. 3.Institute of Human GeneticsUniversity of Erlangen-NurembergErlangenGermany

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